Melanoma drug monotherapy shows promise in phase I trial

LONDON (Reuters) – GlaxoSmithKline’s experimental drug dabrafenib may add months to the lives of melanoma patients with brain metastases, according to data from an early-stage trial published today in The Lancet.

Dabrafenib blocks the activity of a cancer-causing mutated BRAF gene, which is found in about half of melanoma cases. Results released earlier this week from a separate melanoma trial looking at dabrafenib in combination with another GSK drug, trametinib, were also positive.

Researchers said the results of the dabrafenib-only trial, although early-stage, represented an important step forward in the treatment of this deadly cancer. “Dabrafenib is the first drug of its class to show activity in treatment of melanoma brain metastases,” according to the report.

Georgina Long of the Melanoma Institute Australia and Westmead Hospital in Sydney, and Gerald Falchook from the University of Texas in the United States, treated 184 patients with dabrafenib in the phase I dose-finding trial, including 156 with metastatic melanoma.

They said some of the most exciting results came from a subset of 10 patients whose tumors had spread to their brains. These ten were among 36 patients who received150 mg twice daily, the amount recommended for the phase II trial.

None of these had previously received treatment for their brain tumors. However, the brain metastases disappeared in four of the patients. Five patients saw their brain metastases shrink, and one had stable disease.

“The results in the brain were remarkable,” Long said. “I don’t think there is a single other systemic agent that is as active in the brain.”

Experts not involved in the trial also said the drug showed promise.

In a commentary in The Lancet, Geoffrey Gibney and Vernon Sondak from the H. Lee Moffitt Cancer Center and Research Institute in the U.S. described the results as “impressive” and “encouraging.”

Long and Falchook said it was not clear why the drug was so effective in the brain where other drugs have failed, but further trials are underway to try to clarify the mechanism.

“The big message is that the brain, with this drug, is just like another organ,” Long said. “If you are going to respond in your lung and liver, you tend to respond in your brain as well.”

Unfortunately, for most of the patients with brain metastases, the response to the drug was limited to several months.

Long said, however, these few months of extension of life were very rare in patients with melanoma that has spread to the brain. Normally, such patients can only expect to survive for four months from the point of diagnosis, she said.

“With this drug, these patients had no progression of their disease for a median of 4.2 months. Without treatment, many of them might already have died at that point,” she said.

Two of the 10 brain metastasis patients who received the drug survived for more than 12 months. One was still alive and receiving the drug at 19 months.